Coadministration of QIV-HD Influenza Vaccine, mRNA-1273 COVID-19 Vaccine Is Safe

Doctor giving patient vaccine, flu or influenza shot or taking blood test with needle. Nurse with injection or syringe. Medicine, insulin or vaccination. Hospital office room.
Researchers examined the safety and immunogenicity of administering a high-dose quadrivalent influenza vaccine and a third dose of mRNA-1273 vaccine booster concomitantly.

Concomitant administration of the high-dose quadrivalent influenza vaccine (QIV-HD) and the mRNA-1273 SARS-CoV-2 vaccine booster dose is not associated with any safety concerns or interference in older adults’ immune response, according to interim results from an ongoing phase 2 clinical trial published in The Lancet Respiratory Medicine.

The multicenter, open-label, descriptive trial ( Identifier: NCT04969276) is being conducted at 6 clinical research sites in the United States. All community-dwelling adults aged 65 years or older who previously received a 2-dose primary schedule of the mRNA-1273 SARS-CoV-2 vaccine were eligible for inclusion in the study. The second dose of the primary mRNA-1273 vaccination series needed to have been administered at least 5 months prior to study enrollment.

All of the study participants were randomly assigned in a 1:1 ratio (via use of a permuted block method stratified by site and age-group [<75 years vs ≥75 years]) to receive 1 of the following: (1) concomitant administration of QIV-HD and the mRNA-1273 vaccine; (2) QIV-HD alone; or (3) the mRNA-1273 vaccine alone.

Between July 16 and August 31, 2021, a total of 306 individuals were enrolled in the study and were randomly assigned to 1 of the 3 groups, with 296 of these persons receiving 1 dose or more (n=100 in the coadministration group, n=92 in the QIV-HD-alone group, and n=104 in the mRNA-1273-alone group). Reactogenicity profiles were similar between the coadministration and the mRNA-1273 vaccine groups, with lower reactogenicity rates reported in the QIV-HD-alone group. Solicited injection site reactions that occurred up to 7 days after mRNA-1273 vaccine injection occurred at similar rates in the coadministration group (86.0%  [86 of 100 participants]; 95% CI, 77.6-92.1) and in the mRNA-1273-vaccine-alone group (91.3% [95 of 104 participants]; 95% CI,  84.2-96.0), and at lower rates in the QIV-HD group (61.8% [55 of 89 participants]; 95% CI, 50.9-71.9).

Solicited injection site reactions reported following the QIV-HD injection in the coadministration group occurred less often than those following the mRNA-1273 vaccine injection in the coadministration group (61.0%; 95% CI, 50.7-70.6 vs 82.0%; 95% CI, 73.1-89.0 in the QIV-HD-injected limbs and the mRNA-1273-injected limbs, respectively) and at a similar rate to the QIV-HD-alone group (61.8%; 95% CI, 50.9-71.9). The frequency of solicited systemic reactions was 80.0% (95% CI, 70.8-87.3), 83.7% (95% CI, 75.1-90.2), and 49.4% (95% CI, 38.7-60.2) in the coadministration, mRNA-1273-alone, and QIV-HD groups, respectively.

Up to day 22, unsolicited adverse events (AEs) were reported among 17.0% (95% CI, 10.2-25.8) of participants in the coadministration arm and 14.4% (95% CI, 8.3 to 22.7) in the mRNA-1273-alone arm. Unsolicited AEs occurred at a slightly lower rate (ie, 10.9%; 95% CI, 5.3-19.1) among participants in the QIV-HD-alone arm.

Overall, 7 participants each reported 1 medically attended AE (3 in the coadministration arm, 3 in the mRNA-1273 arm, and 1 in the QIV-HD arm). No serious AEs, AEs of special interest, or deaths were reported. Hemagglutination inhibition antibody geometric mean titers increased from day 1 to day 22 to similar levels in the coadministration and the QIV-HD groups for each influenza strain. Additionally, SARS-CoV-2 binding antibody geometric mean concentrations also increased to levels that were similar in the coadministration and mRNA-1273 arms at day 22 (7634; 95% CI, 6445-9042 vs 7904; 95% CI, 6883-9077, respectively).

“Concomitant implementation of these vaccination campaigns could help avoid potential delays in influenza vaccination during the northern hemisphere influenza season due to prioritization of COVID-19 booster vaccination, which is particularly important among individuals at increased risk of severe illness and hospitalization from both COVID-19 and influenza infection,” the study authors wrote. “Therefore, concomitant vaccination might be needed to reduce morbidity and mortality due to these infectious diseases as much as possible.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Izikson R, Brune D, Bolduc JS, et al. Safety and immunogenicity of a high-dose quadrivalent influenza vaccine administered concomitantly with a third dose of the mRNA-1273 SARS-CoV-2 vaccine in adults aged ≥65 years: a phase 2, randomised, open-label study. Lancet Respir Med. Published online January 31, 2022. doi:10.1016/S2213-2600(21)00557-9